Feasibility Study of SBRT Plus Chemotherapy for Non-Small Cell Lung Carcinoma

Inclusion Criteria:

* Patients must have pathologic diagnosis of non-small cell lung carcinoma (NSCLC), by either histologic biopsy, or cytologic evidence; highly suspicious cytology (i.e. abnormal cells suspicious for malignancy) is acceptable, in the setting of a strongly positive computed tomography (CT)/positron emission tomography (PET) (standardized uptake value \[SUV\] \> 5.0)
* Patients must be considered appropriate for stereotactic body radiation therapy (SBRT); this is determined on an individualized basis, by the prospective multidisciplinary tumor board, that includes representation from surgical, radiation and medical oncology; criteria for appropriateness for SBRT include all of the following:

  * Stage I/II non-small cell lung carcinoma (NSCLC) - no evidence of distant metastases (patients with up to three lung nodules may be considered to have 'multiple primary' lung cancer rather than metastatic lung cancer and thus will be eligible; if a lymph node(s) ≥ 2 cm and/or PET-SUV ≥ 4.0 is identified, biopsy must be performed (and be negative) for the patient to be eligible; patients thought to have M1b disease, or malignant pleural/pericardial effusions are not eligible
  * Staging including CT chest, PET/CT must be up-to-date, i.e. within 6 weeks prior to registration; brain imaging (contrast-enhanced magnetic resonance imaging \[MRI\] or CT) is suggested for all patients, but is only mandatory for patients with abnormal neurologic exam
  * Tumor size ≤ 7 cm in greatest dimension based upon an up-to-date CT (and/or CT/PET) within 6 weeks prior to enrollment onto the study; radiation therapy treatment planning imaging is acceptable)
  * The patient must not be a candidate for (or declines because of high risk) surgical resection because of medical comorbidity/risk; the patient must have undergone an evaluation by an experienced thoracic surgeon within 12 weeks prior to registration; standard justification criteria may include forced expiratory volume in 1 second (FEV1) \< 40% predicted; predicted postoperative FEV1 ≤ 30% predicted; diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 60% predicted; pulmonary hypertension (estimated ≥ 40 mm Hg); poor cardiac function (ejection fraction \[EF\] ≤ 40%); Medical Research Council (MRC) dyspnea scale ≥ 3 (corresponds to inability to walk at least 100 yards without rest); baseline hypoxemia (partial pressure of oxygen \[pO2\] ≤ 55 mg HG and/or pulse oxygen \[ox\] \< 88%), baseline hypercapnia (carbon dioxide \[CO2\] ≥ 45 mm Hg; there are also other, less objective criteria, including severe end-organ damage from diabetes/hypertension, severe atherosclerotic disease (heart, brain, aorta, peripheral artery)
  * Tumor(s) must be in a location/configuration such that risk of fistula is considered relatively low; this means that there can be no evidence of tumor invasion of a major (lobar/hilar) pulmonary vessel(s), aorta, vena cava, trachea or mainstem bronchus or esophagus; additional studies may be needed to assess this, including CT angiogram, MRI, bronchoscopy, esophagoscopy
* One or more of the following "risk" criteria for failure with conventional SBRT treatment alone:

  * Peripheral tumor ≥ 4 cm in any dimension
  * Central tumor (i.e. gross tumor within 2 cm of a major bronchus/vessel, or heart/pericardium), including hilar lymph node(s)
  * Multiple tumors (i.e. satellitosis-defined T3-4, or bilateral synchronous primary lung cancer; note that the maximum number of total lesions allowable on this study for treatment with SBRT is 3 (Three), and all lesions must be amenable to SBRT and treated with SBRT on this study; note that it is not necessary for all lesions felt to be malignant to be biopsied
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
* Hemoglobin ≥ 9.0 g/dl
* Absolute neutrophil count ≥ 1,500/mcL
* Platelet count ≥ 100,000 cells/mcL
* Total bilirubin ≤ 1.5 X institutional upper limit of normal
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 2.5 X institutional upper limit of normal
* Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 X institutional upper limit of normal
* Serum creatinine ≤ 1.5 X institutional upper limit of normal
* Alkaline phosphatase ≤ 2.5 X institutional upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
* Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 6 weeks prior to study entry, for the duration of study participation and for 6 months after completing treatment; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately
* Subjects must have the ability to understand and the willingness to sign a written informed consent document
* Patients must not have grade 2 or greater pre-existing peripheral neuropathy (per Common Terminology Criteria for Adverse Events \[CTCAE\] 4.0)

Exclusion Criteria:

* Prior treatment toxicities (i.e. any toxicity from treatment of a previous cancer ) must be resolved to ≤ grade 1 according to National Cancer Institute (NCI) CTCAE version 4.0 (except alopecia)
* Patients who are receiving any other investigational agents
* Patients with prior invasive malignancy within two years of enrollment are excluded
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) or other agents used in this study
* Patients with severe cardiac disease including symptomatic congestive heart failure, unstable angina, or have experience an acute myocardial infarction within the past 6 months; please note: patients with chronic obstructive pulmonary disease (COPD) are not excluded
* Pregnant or breastfeeding women are excluded from this study; breastfeeding should be discontinued
* Known human immunodeficiency virus (HIV)-positive patients are ineligible